Department of Radiation Oncology, Iridium Netwerk, Wilrijk-Antwerp, Belgium.
Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk-Antwerp, Belgium.
J Natl Cancer Inst. 2021 Oct 1;113(10):1360-1368. doi: 10.1093/jnci/djab113.
Uncertainty about the benefit-risk ratio of regional lymph node irradiation led to varying clinical protocols. We investigated long-term late side effects after internal mammary and medial supraclavicular (IM-MS) lymph node irradiation to improve shared decision making.
The multicenter European Organization for Research and Treatment of Cancer trial (ClinicalTrials.gov, NCT00002851) randomly assigned stage I-III breast cancer patients with involved axillary nodes and/or a medially located primary tumor. We analyzed late side effects both longitudinally at every follow-up and cross-sectionally at 5-year intervals. All statistical tests were 2-sided.
Between 1996 and 2004, 46 departments from 13 countries accrued 4004 patients. Median follow-up was 15.7 years. Longitudinal follow-up data showed cumulative incidence rates at 15 years of 2.9% (95% confidence interval [CI] = 2.2% to 3.8%) vs 5.7% (95% CI = 4.7% to 6.9%) (P < .001) for lung fibrosis, 1.1% (95% CI = 0.7% to 1.7%) vs 1.9% (95% CI = 1.3% to 2.6%) (P = .07) for cardiac fibrosis, and 9.4% (95% CI = 8.0% to 10.8%) vs 11.1% (95% CI = 9.6% to 12.7%) (P = .04) for any cardiac disease when treated without or with IM-MS lymph node irradiation. There was no evidence for differences between left- and right-sided breast cancer (Wald χ2 test of treatment by breast side interaction, P = .33 and P = .35, for cardiac fibrosis and for any cardiac disease, respectively). The cumulative incidence probabilities of cross-sectionally reported side effects with a score of 2 or greater at 15 years were 0.1% (95% CI = 0.0% to 0.5%) vs 0.8% (95% CI = 0.4% to 1.4%) for pulmonary (P = .02), 1.8% (95% CI = 1.1% to 2.8%) vs 2.6% (95% CI = 1.8% to 3.7%) for cardiac (P = .15), and 0.0% (95% CI not evaluated) vs 0.1% (95% CI = 0.0% to 0.4%) for esophageal (P = .16), respectively. No difference was observed in the incidence of second malignancies, contralateral breast cancer, or cardiovascular deaths.
The incidence of late pulmonary side effects was statistically significantly higher after IM-MS lymph node irradiation, as were some of the cardiac events, without a difference between left- and right-sided treatments. Absolute rates and differences were very low, without increased non-breast cancer-related mortality, even before introducing heart-sparing techniques.
由于对区域淋巴结照射的获益-风险比存在不确定性，导致临床方案存在差异。我们研究了内乳和内锁骨上（IM-MS）淋巴结照射后的长期迟发性副作用，以改善共同决策。
这项多中心欧洲癌症研究与治疗组织（EORTC）临床试验（ClinicalTrials.gov，NCT00002851）将累及腋窝淋巴结和/或中央型原发肿瘤的 I 期至 III 期乳腺癌患者随机分组。我们分析了纵向随访时的迟发性副作用和 5 年间隔的横断面随访时的迟发性副作用。所有统计检验均为双侧检验。
1996 年至 2004 年期间，来自 13 个国家的 46 个科室共入组 4004 例患者。中位随访时间为 15.7 年。纵向随访数据显示，15 年时肺纤维化的累积发生率分别为 2.9%（95%置信区间[CI]，2.2%3.8%）和 5.7%（95%CI，4.7%6.9%）（P<0.001），心脏纤维化的发生率分别为 1.1%（95%CI，0.7%1.7%）和 1.9%（95%CI，1.3%2.6%）（P=0.07），任何心脏疾病的发生率分别为 9.4%（95%CI，8.0%10.8%）和 11.1%（95%CI，9.6%12.7%）（P=0.04），未行 IM-MS 淋巴结照射组与行 IM-MS 淋巴结照射组相比。左侧和右侧乳腺癌之间无差异（治疗与乳房侧的交互作用的 Wald χ2 检验，P=0.33 和 P=0.35，分别用于心脏纤维化和任何心脏疾病）。15 年时，横断面上报告的发生率为 2 或更高的副作用的累积发生率概率为 0.1%（95%CI，0.0%0.5%）和 0.8%（95%CI，0.4%1.4%）（P=0.02）用于肺部，1.8%（95%CI，1.1%2.8%）和 2.6%（95%CI，1.8%3.7%）（P=0.15）用于心脏，0.0%（95%CI 未评估）和 0.1%（95%CI，0.0%~0.4%）（P=0.16）用于食管，分别。未观察到第二恶性肿瘤、对侧乳腺癌或心血管死亡的发生率差异。
与未行 IM-MS 淋巴结照射相比，行 IM-MS 淋巴结照射后肺迟发性副作用的发生率统计学上显著更高，部分心脏事件发生率也更高，但左侧和右侧治疗之间无差异。绝对发生率和差异非常低，即使在引入心脏保护技术之前，也没有增加非乳腺癌相关死亡率。
